Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds...

The intergeniculate leaflet (IGL) of the thalamus is a retinorecipient structure implicated in orchestrating circadian rhythmicity. The IGL network is highly GABAergic and consists mainly of neuropeptide Y-synthesising and enkephalinergic neurons. A high density of GFAP-immunoreactive astrocytes has been observed in the IGL, with a probable function in guarding neuronal inhibition. Interestingly, putatively enkephalinergic IGL neurons generate action potentials with an infra-slow oscillatory (ISO) pattern in vivo in urethane anesthetised Wistar rats, under light-on conditions only...

The intergeniculate leaflet (IGL) is a flat thalamic nucleus implicated in the modulation of circadian rhythmicity. In rat, two main GABAergic subpopulations can be distinguished in the IGL: neurons synthesizing neuropeptide Y (NPY), which directly innervates the suprachiasmatic nuclei, and enkephalinergic cells, which connect contralaterally located leaflets. The aim of this study was to evaluate possible effects of inner IGL neurotransmitters on the spontaneous and synaptic activity of IGL neurons. The data presented in this article provide evidence that enkephalin, and not NPY, could act upon the majority of IGL neurons...

Several studies suggest that prenatal ethanol exposure (PEE) facilitates ethanol intake. Opioid peptides play a main role in ethanol reinforcement during infancy and adulthood. However, PEE effects upon motor responsiveness elicited by an ethanol challenge and the participation of opioids in these actions remain to be understood. This work assessed the susceptibility of adolescent rats to prenatal and/or postnatal ethanol exposure in terms of behavioral responses, as well as alcohol effects on Met-enk expression in brain areas related to drug reinforcement...

Neuropathic pain remains difficult to treat due to the involvement of various pathophysiological mechanisms in its pathogeny. Among the different opioidergic systems the enkephalinergic one is primarily recruited via activation of delta opioid receptor (DOP) in chronic pain and of mu opioid receptor (MOP) in acute pain. To investigate the role of their endogenous ligands Met and Leu-enkephalin in neuropathic pain control, a dual inhibitor of their degrading enzymes, PL265, which acts restrictively at the level of peripheral nociceptors, was administered per os to assess its efficacy in pain prevention and alleviation using a partial sciatic nerve ligation model (PSNL) in mice...

The intergeniculate leaflet (IGL) is a flat retinorecipient thalamic structure implicated in orchestrating circadian rhythm, historically considered to be a subdivision of the neighboring ventrolateral geniculate nucleus (VLG). IGL consists of two main neuronal subpopulations: enkephalinergic and neuropeptide Y (NPY)-synthesizing cells. These cell types have different functions, connectivity and firing pattern in vivo, which suggest that they have different membrane currents to support their functional differences...

Human female reproductive system is closely dependent by hormonal stimulation. Anyway it is now commonly stated that autonomic innervation system regulates, along with hormonal stimulation, the uterine physiology. Cholinergic and adrenergic innervations have a critical role in mediating input to the uterus, but other neurotransmitters and neuropeptides exist that influence uterine physiology, as well. In the present investigation, we analyzed the uterine distribution of a large set of neurotransmitters, focusing on adrenergic, noradredenergic, acetylcholine (AChE) positive, dopaminergic, serotoninergic and peptidergic neurofibers; among these latter, we focused on those releasing prolattine, enkephalines (ENKs), Vasoactive Intestinal Polypeptide (VIP), substance P (SP) and oxytocine...

Primary pain and touch sensory neurons not only detect internal and external sensory stimuli, but also receive inputs from other neurons. However, the neuronal derived inputs for primary neurons have not been systematically identified. Using a monosynaptic rabies viruses-based transneuronal tracing method combined with sensory-specific Cre-drivers, we found that sensory neurons receive intraganglion, intraspinal, and supraspinal inputs, the latter of which are mainly derived from the rostroventral medulla (RVM)...

GABA and enkephalin provide significant innervation of sympathetic preganglionic neurons. Despite some investigation as to the identity of premotor sources of these innervations no comprehensive analyses have been conducted. Similarly, although data describing the cardiovascular effects of blockade of GABAA receptors in the spinal cord is available, the effects at other sympathetic outflows are unknown. In contrast the sympathetic effects of opioid blockade in the spinal cord are unclear. The aims of this study were to identify potential sympathetic premotor sources of GABAergic and enkephalinergic input to the spinal cord and to describe the sympathetic and cardiovascular effects of spinal GABAA receptor and delta/mu opioid receptor blockade in urethane anaesthetised rats...

While previous studies and brain atlases divide the hypothalamus into many nuclei and areas, uncharacterised regions remain. Here, we report a new region in the mouse anterior hypothalamus (AH), a triangular-shaped perifornical area of the anterior hypothalamus (PeFAH) between the paraventricular hypothalamic nucleus and fornix, that abundantly expresses chondroitin sulfate proteoglycans (CSPGs). The PeFAH strongly stained with markers for chondroitin sulfate/CSPGs such as Wisteria floribunda agglutinin and antibodies against aggrecan and chondroitin 6 sulfate...

Enkephalinergic neuroendocrine-immune regulatory system is one of the most important neuroendocrine-immune systems in both vertebrates and invertebrates for its significant role in the immune regulation. In the present study, the early onset of enkephalinergic nervous system and its immunomodulation on the developing immune system during the ontogenesis of oyster Crassostrea gigas were investigated to illustrate the function of neural regulation on the innate immune system in oyster larvae. [Met(5)]-enkephalin (Met-ENK) was firstly observed on the marginal of the dorsal half of D-hinged larvae...

Scallops are a cosmopolitan family of bivalves, and some of them are highly prized as dominant aquaculture species. In the past decades, there have been increasing studies on the basic biology and immunology of scallops, and this review summarizes the research progresses of immune system and its modulation mechanism in scallop. As invertebrate, scallops lack adaptive immunity and they have evolved an array of sophisticated strategies to recognize and eliminate various invaders by employing a set of molecules and cells...

Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function...

UNLABELLED: Rats selectively bred for high- and low-capacity for running on a treadmill (HCR; LCR) also differ in wheel-running behavior, but whether wheel-running can be explained by intrinsic or adaptive brain mechanisms is not as yet understood. It is established that motivation of locomotory behavior is driven by dopaminergic transmission in mesolimbic and mesostriatal systems. However, whether voluntary wheel running is associated with enkephalinergic activity in the ventral striatum is not known...

The dorsal raphe nucleus (DRN) is involved in the control of several physiological functions, including nociceptive modulation. This nucleus is one of the main sources of serotonin to the CNS and neuromodulators such as opioids and GABA may be are important for its release. This study evaluated the influence of serotonergic, GABAergic and opioidergic stimulation, as well as their interactions in the DRN, on vocalization nociceptive response during a peripheral noxious stimulus application in guinea pigs. Morphine (1...

Activation of mu-opioid receptor (MOR) disinhibits dopaminergic neurons in the ventral tegmental area (VTA) through inhibition of γ-aminobutyric acid (GABA)ergic neurons. This mechanism is thought to play a pivotal role in mediating reward behaviors. Here, we characterised VTA-projecting enkephalinergic neurons in the anterior division of the bed nucleus of the stria terminalis (BST) and investigated their targets by examining MOR expression in the VTA. In the BST, neurons expressing preproenkephalin mRNA were exclusively GABAergic, and constituted 37...

Enkephalin (ENK) has been postulated to play important roles in modulating nociceptive transmission, and it has been proved that ENKergic neurons acted as a critical component of sensory circuit in the adult spinal cord. Revealing the developmental characteristics of spinal ENKergic neurons will be helpful for understanding the formation and alteration of the sensory circuit under pain status. However, the relationship between the embryonic birth date and the adult distribution of ENKergic neurons has remained largely unknown due to the difficulties in visualizing the ENKergic neurons clearly...

Although it is a general consensus that opioids modulate growth, the mechanism of this phenomenon is largely unknown. Since endogenous opiates use the same receptor family as morphine, these peptides may be one of the key regulators of growth in humans by impacting growth hormone (GH) secretion, either directly, or indirectly, via growth hormone-releasing hormone (GHRH) release. However, the exact mechanism of this regulation has not been elucidated yet. In the present study we identified close juxtapositions between the enkephalinergic/endorphinergic/dynorphinergic axonal varicosities and GHRH-immunoreactive (IR) perikarya in the human hypothalamus...

The endogenous opioid enkephalin is known to inhibit spinal nociceptive transmission. Here we investigated activation of spinal enkephalinergic neurons by determining the proportions of c-Fos expressing (activated) spinal neurons that were enkephalinergic after different acute and chronic peripheral nociceptive stimuli. The number of c-Fos-activated neurons in the dorsal horn was increased after hind paw injection of capsaicin, formalin or complete Freund's adjuvant (CFA, 1.5 hrs - 4 days). The numbers of these neurons that were enkephalinergic increased after paraformaldehyde, and at 20 hrs, but not 1...

The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to cause striatopallidal neuron vulnerability in early-stage Huntington's disease. Although several studies have confirmed a link between altered cortical brain-derived neurotrophic factor signaling and striatal vulnerability, it is not known whether the effects are mediated via the brain-derived neurotrophic factor receptor TrkB, and whether they are direct or indirect...